Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction
Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction
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DOI：
10.1016/j.jsxm.2021.06.004
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发表时间：
2021-08-02
影响因子：
3.5
通讯作者：
Kimura, Kazunori
中科院分区：
文献类型：
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作者：
Kataoka, Tomoya;Mori, Taiki;Kimura, Kazunori
背景：化疗是目前国际上治疗癌症的标准方案之一，化疗药物具有多种不良反应，包括勃起功能障碍(ED)。目的：观察抗癌药物奥沙利铂(L-OHP)对大鼠勃起功能的影响。方法：雄性Wistar/ST大鼠随机分为2组：L-OHP组(n=21)，静脉注射L-OHP(4 mg/kg，每周2次，连续4周)；对照组(n=21)，按相同的给药程序，注射等量5%葡萄糖溶液。治疗结束后(n=9~10)测定海绵体内压(ICP)和海绵体神经刺激后平均动脉压(MAP)。使用海绵体条行等长张力研究(n=11)评价血管内皮功能。免疫印迹法检测神经元型一氧化氮合酶(NNOS)和内皮型一氧化氮合酶(ENOS)蛋白水平(n=7)。实时定量聚合酶链式反应(qRT-PCR)检测炎症和氧化应激相关标志物(烟酰胺腺嘌呤二核苷酸磷酸氧化酶-1、p22(Phox)、白介素IL-6和核因子-kappaB)的表达(n=6)。结果：L-OHP组的颅内压/平均动脉压比值明显低于对照组(P
Background: Chemotherapeutics, one of the standard treatment options for cancer worldwide, have various adverse effects, including erectile dysfunction (ED).Aim: To investigate erectile function in an animal model after administration of the anticancer agent oxaliplatin (L-OHP).Methods: Male Wistar/ST rats were divided into 2 groups: L-OHP rats (n = 21), which were intravenously administered L-OHP (4 mg/kg; twice a week for 4 weeks), and Control rats (n = 21), which were injected with the same volume of 5% glucose solution, using the same dosing schedule. At the end of the study period, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation (n = 9-10). Endothelial function was evaluated with an isometric tension study using corpus cavernosum strips (n = 11). Western blot analysis was used to assess neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS) protein levels (n = 7). Real-time quantitative polymerase chain reaction (qRT-PCR) was used to assess the expression of inflammation- and oxidative stress-related markers (nicotinamide adenine dinucleotide phosphate oxidase-1, p22(phox), interleukin [IL]-6, and nuclear factor-kappa B) (n = 6). Statistical significance was determined using the Student's t-test.Outcomes: The L-OHP group had a significantly lower ICP:MAP ratio than the control group (P